The use of human ultralente is limited by great intraindividual variability in overnight plasma insulin profiles

Our objective was to investigate the usefulness of human ultralente insulin as basal substitution overnight in patients with Type 1 diabetes treated with multiple insulin injection therapy by evaluating the free insulin and glucose profiles, the day-to-day variability and the impact of the time of injection. Methods: Ten patients with Type 1 diabetes and with good metabolic control (mean HbAlc 6.0%), treated with regular human insulin before breakfast, lunch and dinner and human ultralente (Ultratard(R)) before dinner or at bedtime, were studied. Plasma profiles of blood glucose and free insulin were measured on three occasions from 16.00 h until noon the next day. On two of these occasions Ultratard(R) was injected before dinner and once it was injected at bedtime in randomized order. Results: Injection of regular insulin before dinner resulted in a high insulin peak during the evening but no insulin peak was found that could be attributed to ultralente. The plasma concentration of free insulin at 03.00 h was 11.0+/-1.9 mU/L and it slowly decreased to 6.4+/-1.4 at 12.00 h after administration of ultralente at 17.00 h. There were no differences in the mean plasma insulin profiles compared to the other occasion when insulin was given at 17.00 h or at 22.00 h. On the other hand, the intra-individual day-to-day variability of mean insulin concentration during the night was considerable, often exceeding 50%. No differences were noted in the mean blood glucose profiles between the three occasions. Conclusion: Human ultralente insulin gives an insulin profile suitable for overnight substitution, but the great day-to-day variability limits its usefulness. It can be injected before dinner or at bedtime without any change in the insulin profile during the night.